This proposal responds to RFA-DK-13-507, which requests applications from existing Discovery Sites participating in the Multi-Disciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Our team at the University of Washington Discovery Site seeks continuing support to participate in efforts to unravel the enigma of urologic chronic pelvic pain syndromes (UCPPS). We will conduct the required Project 1, the Trans-MAPP UCPPS Symptom Pattern Study, and capitalize on our findings from our twin studies and our cohort of UCPPS patients. This large study is a longitudinal investigation of UCPPS symptom patterns and phenotypic features that will provide a platform for standardized recruitment and phenotyping on which to base our other 3 projects. Project 2 will design new clinical tools for patient reporting that can be evaluated by rigorous scientific methods. Project 3 builds on exciting preliminary findings from our study of monozygotic twins who are discordant for interstitial cystitis symptoms. In Project 3, we will use functional magnetic resonance imaging of the brain to examine neural connectivity among UCPPS patients and healthy controls before and during the application of a fluid challenge paradigm to provoke urinary pain. Project 4, which is also informed by findings from our twin study, is basic science/translational work that evaluates epigenetic, telomeric, and bioinformatics approaches in urinary epithelial cells and blood specimens to identify biomarkers for UCPPS diagnosis, disease activity, natural history, and predictors of symptom change. Therefore, our overarching Specific Aims are to 1) Correlate clinically significant longitudinal urological and non-urological symptom patterns with phenotypic characteristics among patients with UCPPS; 2) Create patient-centered clinical tools, including aids to attain treatment goals, electronic patient dashboards, and smartphone symptom diaries that are relevant to providers and both useful and satisfying for UCPPS patients; 3) Ascertain whether particular brain structures are associated with urinary urgency and pain, and compare functional brain connectivity in people with and without chronic urological pelvic pain; and 4) Compare methylation patterns and leukocyte telomere length in UCPPS patients and healthy controls. All projects are designed to be exported to other Discovery Sites. The MAPP Network has transformed the study of UCPPS by encouraging researchers to adopt a broad, systemic view of UCPPS and use novel, multidisciplinary approaches in basic, translational, and clinical science. However, much still remains to be learned about the etiology and natural history of UCPPS, and about the best ways to measure symptoms and outcomes. Our proposed Discovery Site will link clinical epidemiology with basic and translational science in interdisciplinary research of the highest scientific and programmatic caliber.